Introduction: The Levine model of hypoxic-ischemic encephalopathy (HIE) was invesigated using dynamic interleaved diffusion MRI and perfusion weighted MRI, using an intravascular iron containing blood pool contrast agent. Methods: New Zealand white rabbits (8-14 days old, n=7) were anesthetized with Halothane and one common carotid artery (CCA) was ligated. A plastic nose cone allowed variable FiO2 administration by nitrogen dilution. MRI was performed using snapshot echo planar imaging (EPI). Interleaved T2 and diffusion weighted EPI images were acquired continuously during HIE. Iron Dextran was injected to sensitize T2-wt. images to changes in blood volume. Serial apparent diffusion coefficient (ADC) and relative CBV maps were generated every 9 seconds. After contrast injection, animals were exposed to 10% FiO2. Hypoxia was reversed when reduced ADC was observed over the entire ipsilateral hemisphere. Results: Immediately post-hypoxia there was globally increased CBV. In 2 animals diffusion abnormalities appeared soon after the onset of hypoxia then rapidly progressed to global ischemia. Animals then suffered cardiac arrest. In 5 animals, diffusion changes appeared focally and spread more slowly over the ipsilateral cortex. These changes rapidly reversed upon return to normoxia. Concurrent with the focal ADC drop, there was a localized CBV decrease in the same regions, which returned to baseline on normoxia. In 80% of animals, MABP increased upon hypoxia, decreased to around baseline, then slowly decreased with prolonged hypoxia. In the remaining animals the MABP stayed at baseline value after the initiation of hypoxia and slowly decreased with continued hypoxia. Conclusions: Dynamic concurrent diffusion/CBV MRI is a sensitive means of monitoring the acute hemodynamic and metabolic related effects of HIE in vivo.